1. Field of the Invention
The present invention relates to fluorescent imaging devices to conduct fluorescent observations by using an endoscope to irradiate an excitation light onto an area of a biological tissue to be examined with such devices being characterized by the ability to switch between fluorescent observation and a conventional reflected light observation.
2. Description of the Related Art
Recently, diagnostic techniques have been developed using an endoscope to irradiate tissue to be studied with visible light and to detect resulting fluorescent images which are then analyzed for diagnostic purposes. These techniques have been found particularly useful for diagnosing disease conditions such as cancers or tissue degeneration and for highlighting the boundary regions of the conditions under study. These techniques are sometimes enhanced by also studying normal light images resulting from reflection of the irradiating visible light (usually white light).
In the case of autofluorescence, i.e., the stimulated emission resulting from impingement of the excitation light onto a biological tissue, the fluorescence typically has a longer wavelength than that of the excitation light. Fluorescent substances within organisms are exemplified by collagens, NADH (nicotinamide adenine dinucleotide), FMN (flavin mononucleotide), pyridine nucleotide and the like. Recently, the relationship between such fluorescent substances and various diseases has been recognized, making it possible to diagnose cancers and the like by these fluorescences.
In addition, certain fluorescent substances such as HpD (hematoporphyrin), Photofrin, ALA (xcex4-amino levulinic acid), and GFP (Green fluorescent protein), have been found which are selectively absorbed by cancers and thus may be used as contrast materials. In addition, certain fluorescent substances may be added to a monoclonal antibody whereby the fluorescent may be attached to affected areas by an antigen-antibody reaction.
As the excitation lights, for example, lasers, mercury lamps, metal halide lamps and the like are used. For example, when a light with the wavelength of 437 nm is emitted onto a gastrointestinal tract tissue, green autofluorescence by abnormal tissues is attenuated compared to the autofluorescence of normal tissues, but red autofluorescence of abnormal tissues is not attenuated as much compared to the autofluorescence of normal tissues. A transendoscopic fluorescent observation device utilizing this principle to image the green and red fluorescent emission, and to show the existence of abnormal tissues has been disclosed in Japanese Unexamined Patent Publication No. 9-327433.
Since the fluorescent images obtained in this way have very weak intensities compared to the reflected images obtained with conventional white light, photomultiplication, for example, using an image intensifier is necessary.
Generally, when a blue or ultraviolet light is emitted onto biological tissue, an autofluorescence occurs within a longer wavelength band than that of the excitation light. Moreover, fluorescent spectra are different between normal tissues and abnormal tissues such as precancerous tissues, cancerous tissues, inflammatory tissues, and dysplastic tissues so that the existence of lesions and conditions of lesions can be detected based on the changes in delicate coloration of the fluorescent images.
In particular, since with a blue excitation light, the intensity distribution of fluorescence stimulated near the green region, especially that of 490 nm-560 nm, is stronger in normal tissue than in diseased tissue, emissions in the green region and in the red region, e.g., wavelengths in the 620 nm-800 nm region are arithmetically processed to generate two-dimensional fluorescent images, and by these fluorescent images the discrimination between affected areas and normal areas can be achieved.
Video images are produced for diagnostic observation of the autofluorescent emissions, and adjustments are made to the ratio between the video signals corresponding to the green and red fluorescent intensities to allow normal tissues to have a certain color tone. Accordingly, tissue known to be normal is first observed, and the ratios of the red and green emissions are adjusted to establish a reference color tone. Then, after the adjustment of the color tone of the normal parts, the potentially diseased tissue is observed. In this way, the normal parts are designated with a certain color tone and abnormal parts are designated with different color tones from that of the normal parts due to the attenuation of the green signal. By the differences in color tones between abnormal and normal parts, the abnormal parts can be visualized. Typically, the ratio is adjusted so that the normal tissue appears a cyanic color tone and diseased tissue appears a red color tone.
Moreover, in a fluorescent observation device of Japanese Unexamined Patent Publication No. 8-557, a single light source is used both as an excitation light to conduct fluorescent observations and as a white light to conduct white light observations by insertion and removal of a filter. Endoscopes usually also include an emergency light source which permits safe removal of the instrument in case of failure of the main light source.
As will be understood, when only fluorescent images are desired, there should be no illumination by white light, but only by the excitation light. Thus, switching is required so that when a white light image is to be obtained, a white light is emitted, and when a fluorescent image is to be obtained, an excitation light is emitted.
Also, switching is controlled so that, when white light is emitted, the resulting image is provided only to a white image imaging device, and when the excitation light is emitted, the fluorescent image is provided only to the high-sensitivity fluorescent imaging device. However, with conventional fluorescent imaging devices, since the endoscope is out of the body when power is applied, if the device is accidently set in its fluorescent observation mode, ambient light may impinge on the fluorescent imaging device. Then, an excess of light enters the image intensifier, and overprint at the high-sensitivity imaging plane of the image intensifier occurs, resulting in its breakdown.
Also with the fluorescent observation device of said Japanese Unexamined Patent Publication No. 8-557, in the case of lamp failure during fluorescent observation, the emergency light provides insufficient luminous energy to excite the tissue sufficiently, making it difficult to observe fluorescence. In addition, even with the emergency light, if the filter for excitation light generation is carelessly removed from in front of the emergency light, the image intensifier will be burnt.
Moreover, since the delicate variations in coloration of fluorescent images are subjectively visualized by the operator, the lack of fixed discrimination standards makes it difficult to compare of findings by different users, and at different facilities such as hospitals.
Also in the conventional example in Japanese Unexamined Patent Publication No. 9-327433, since adjustment of color tone for normal parts is performed on the individual judgment of the user, the absence of fixed calibration standards renders objective diagnosis by color tone difficult.
One object of the present invention is to provide a fluorescent imaging device which protects a fluorescent image high-sensitivity imaging measure even under a transitional condition such as at the power input.
Another object of the present invention is to provide a fluorescent imaging device which prevents damage to the high-sensitivity camera if the normal emitting lamp fails during a fluorescent observation and is replaced by the emergency light.
Still another object of the present invention is to provide a fluorescent imaging device which objectively discriminates against delicate changes in coloration of fluorescent images so that an operator can easily visualize the existence of lesions and conditions of the lesions.
A further object of the present invention is to provide a fluorescent imaging device which adjusts the color tone of normal tissues to a desired tone by conducting a simple operation during the observation of the normal tissue, while displaying the color tone of abnormal tissue in contrast with the color tone of the normal tissues.
The fluorescent imaging device of the present invention has a light source, which selectively switches between an excitation light and a white light, introduces the light into a light guide, and then emits the light onto the tissue being inspected; a high-sensitivity fluorescent device for fluorescent images; a white image imaging device for white light images; a device which couples the fluorescent image to the fluorescent imaging device, a device which prevents overprint on the high-sensitivity imaging plane of the fluorescent imaging device, a visible image generation device which generates an electric signal output from the fluorescent imaging device, and a separate visible image generation device which generates an electric signal output from the white light image imaging device.